Mandë Holford – The Power of Venom and How it Could One Day Save Your Life.

How does a sea snail catch a fish? I mean, it's a snail, so it's slow, and the fish is not. But yet, this happens. Hidden under the sand is a cone snail. And that orange thing you see is kind of like a tongue.

We call it a proboscis. It uses that to track and subdue this unsuspecting fish. In this predator-prey interaction, these are clearly not your garden variety escargots. These are assassins of the sea.

And their weapon of choice is venom. Venom, like the venom you find in venomous snakes and scorpions, these sea snails, they use their venom to subdue fish, worms and other snails. And the venom of these snails, it's not just one thing, it's actually a cocktail of toxic molecules that are packaged and delivered through a false tooth called a radula.

You can think of the radulas as hypodermic needles. Now, no need to worry, these snails are practicing good needle habits, because each radula is only used once. Now from your own knowledge about venomous organisms, and the keep-you-up-at-night fish-killing video that I just showed you, you might think that venom is dangerous and all bad.

Well, yes and no. A more accurate way of thinking of venom is to think of it as both a supervillain and a superhero. In my lab, we study the evolution of venom in these sea snails as a force for good.

Sounds like a stretch, or maybe even snake oil, but actually, while there are snakes involved, the product is legit. One reason the venom product is so successful is that it transforms a physical warfare into a biochemical one.

Where usually the predator-prey interaction is one of brute force, venom takes it to a molecular scale. And it's not size that matters, but the mixture of your venom arsenal. The chemistry of the toxins in your arsenal is what's going to enable David to conquer Goliath.

And in our scenario, David is clearly the snail. Another feature of venom that makes it so successful is that the toxins work with the precision of a Swiss Army knife. And so these toxins, they come for strongholds that help an organism to function.

So they target blood, brain and membranes. Whether it’s snail venom or snake venom, they each have components that can do things like cause your blood to clot, what we call “hemotoxic.” Or they cause neurons in your brains to not function normally, what we call “neurotoxic.”

Or they have toxins that will poke holes into the membranes of your cells, causing them to rupture and, basically, explode, what we call “cytotoxic.” Cellular explosion, people. Now, if that is not all powerful and all present, nothing is.

Now a little about me, and why I'm so obsessed with venom. I grew up in New York City with forced access to the Natural History Museum. I say "forced access," because I'm one of five kids, and my parents used museums as a form of childcare.

There were two rules: Don't lose anybody and meet Mom and Dad at the African elephants at 5:30, when the museum closes. Those totally unsupervised days running through the halls of the museum were full of adventure and exploration.

And that's how I feel when I'm studying venom. It's a scientific adventure. We're boldly exploring this entity that connects nature and humanity. Another reason that I'm obsessed with venom is because of its duality.

When you inject the components of a venom arsenal into an organism, it can kill or it can cure. At a molecular level, several things can happen. You saw one thing, paralysis in the fish. Now that was happening because the toxins in the venom were attacking how the fish's cells communicate with each other, preventing it from swimming away.

Are there other things that I would like to use venom to attack? For sure. And one of those is cancer. Cancer tumors are cells. And like all cells, they communicate with themselves and their environment around them.

So we would like to find venom components that are very good at disrupting how the tumor cells communicate. Similar to how the venom disrupted how the fish cells communicated and the fish couldn't swim away.

In my lab, we study cancer as a channelopathy. What this means is, basically, we're looking for venom components that will target channels that are overexpressed in tumor cells versus normal cells.

The cancer that we're most focused on right now is liver cancer. And that's because since the 1980s, the death rate of liver cancer has doubled, and it's an emerging threat in the US. In a screen in which we had cervical, neuroblastoma, prostate and liver cancer cells, we found a compound from a terebrid snail that seems to attack liver cancer cells, and only liver cancer cells, and none of the others that were tested.

And then, when we took this compound and we injected it into mouse models that were expressing liver cancer cells, it significantly inhibited the growth of the tumors. We're not quite sure how this works yet, we're still investigating the mechanism and how we can make this compound more effective, so you can't rush out to the pharmacy and order up a killer snail liver-cancer therapy treatment.

Not yet. Basically, what we think is happening is that the compound is blocking a specific channel, prohibiting the transmission of a specific chemical that leads to downstream signaling that enables the tumor to multiply and draw blood to itself.

What we're doing in studying the components of venom to find treatments for human diseases and disorders, is not new, it's what we call natural products drug discovery, and it's been happening for centuries, and in cultures all over the world.

Venoms are not only giving us cool new compounds, but they're also giving us new ways of thinking about how we treat human diseases and disorders. And I'll give you three examples. The first is from killer snails, of course.

And so the first drug from these snails that is on the market is called ziconotide, or Prialt, and it's used to treat chronic pain in HIV and cancer patients. Prialt is a nonaddictive pain therapy.

Three magic words when you think about how we're treating pain currently. We're using things that have a huge cost of addiction. So think of morphine or think of any of your favorite opioid out there.

What the snails have done is they've shown us a way to treat pain without the addiction, which is huge. The next example comes from the Brazilian pit viper. From these snakes, we've derived a compound called captopril.

Captopril is used to treat high blood pressure, and captopril is a breakthrough drug. But not only in and of itself, but because it advanced a whole class of drugs, what we know as ACE inhibitors, which are the most commonly [prescribed] for treating hypertension and heart failure.

The last example is from the Gila monster. And this is a really exciting example of understanding the ecology of these organisms, and pairing it with efficient drug discovery. And Gila monsters are binge eaters.

So when they bite into a large meal, they release things in their venom that lower blood sugar. So what's the drug that you think we found from the Gila monster? A compound that is used to lower the blood sugar in diabetic patients.

Now these are three marvelous examples, but we've just scratched the surface. There's so much more venom out there for us to study. In fact, we think that 15 percent of all the animals on the planet are venomous.

And I think this is a low estimate, given the fact that we haven't surveyed all the animals on the planet. But nature seems to have found something that she likes, and she's repeated it over and over and over again, leading to the vast array of animals that we see around us and all throughout the tree of life.

So whether we're talking about my fave, killer snails, or jellyfish, or the larvae of butterflies and moths, or platypus or slow lorises, whether by sea, land or air, you're sure to encounter a venomous creature.

Remember when I told you that venom can be both a superhero and a supervillain, and you doubted me? Mhm. We're in a race to harness all of this venom goodness before we lose the vast majority of animals on our planet.

It's a holistic process. You can't have the therapeutic treatments without having the animals. And you can't have the animals without having their ecosystems. So for me and the snails, what it means is we have to save the oceans.

And because venomous animals are found everywhere, we basically have to save the planet. So do it for the venomous animals, if you don't want to do it for yourself. And who knows, some day, snail venom might just save your life.

Becoming Smart!

It is said that with age comes wisdom. As a "senior" I would candidly say that were I able to live my life over again but retain all of the lessons that I have learned in my life, then the new, young me would enjoy a very different life than that which I have enjoyed. Experiences (good and bad) teach us life's lessons if you apply them. My intention with this blog is to provide a constant source of wisdom to you, gentle reader, in the hope that you can avoid some or more of life's mistakes and thus enjoy a better quality of life. My sources are global because applied wisdom is what counts.

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